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J. Biol. Chem., Vol. 280, Issue 4, 2691-2699, January 28, 2005
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¶
From the
Institut für Genetik and
Zentrum für Molekulare Medizin, Universität zu Köln, 50674 Köln, Germany
Conserved ATP-dependent proteases ensure the quality control of mitochondrial proteins and control essential steps in mitochondrial biogenesis. Recent studies demonstrated that non-assembled mitochondrially encoded proteins are degraded to peptides and amino acids that are released from mitochondria. Here, we have characterized peptides extruded from mitochondria by mass spectrometry and identified 270 peptides that are exported in an ATP- and temperature-dependent manner. The peptides originate from 51 mitochondrially and nuclearly encoded proteins localized mainly in the matrix and inner membrane, indicating that peptides generated by the activity of all known mitochondrial ATP-dependent proteases can be released from the organelle. Pulse-labeling experiments in logarithmically growing yeast cells revealed that
612% of preexisting and newly imported proteins is degraded and contribute to this peptide pool. Under respiring conditions, we observed an increased proteolysis of newly imported proteins that suggests a higher turnover rate of respiratory chain components and thereby rationalizes the predominant appearance of representatives of this functional class in the detected peptide pool. These results demonstrated a constant efflux of peptides from mitochondria and provided new insight into the stability of the mitochondrial proteome and the efficiency of mitochondrial biogenesis.
Received for publication, September 15, 2004 , and in revised form, November 5, 2004.
* This work was supported by grants from the Deutsche Forschungsgemeinschaft (to T. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental material.
¶ To whom correspondence should be addressed: Institut für Genetik, Universität zu Köln, Zülpicher Str. 47, 50674 Köln, Germany. Tel.: 49-221-470-4876; Fax: 49-221-470-6748; E-mail: Thomas.Langer{at}uni-koeln.de.
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